Functional Evolution of Cardiac MicroRNAs in Heart Development and Functions

MicroRNAs are a class of endogenous small noncoding RNAs that regulate gene expression either by degrading target mRNAs or by suppressing protein translation. MicroRNAs have been found to be involved in many biological processes, such as development, differentiation and growth. However, the evolution of microRNA regulatory functions and networks has not been well studied. In this study, we conducted a cross-species analysis to study the evolution of cardiac microRNAs and their regulatory functions and networks. We found that conserved cardiac microRNA target genes have maintained highly conserved cardiac functions. Additionally, most of cardiac microRNA target genes in human with annotations of cardiac functions evolved from the corresponding homologous targets which are also involved in heart development related functions. Based on these results, we investigated the functional evolution of cardiac microRNAs and presented a functional evolutionary map. From this map, we identified the evolutionary time at which the cardiac microRNAs became involved in heart development or function and found that the biological processes of heart development evolved earlier than those of heart functions, e.g., heart contraction/relaxation or cardiac hypertrophy. Our study of the evolution of the cardiac microRNA regulatory networks revealed the emergence of new regulatory functional branches during evolution. Furthermore, we discovered that early evolved cardiac microRNA target genes tend to participate in the early stages of heart development. This study sheds light on the evolution of developmental features of genes regulated by cardiac microRNAs.